The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation and plays a gate keeper role in the control of cell cycle progression and mediates mitogenic signals from P13K/AKT through to the downstream targets S6K1 and 4E-BP1 and to Ser 473 on AKT. Recently it has been shown that mTOR exists in two complexes, raptor-mTOR complex (mTORC1), a rapamycin-sensitive complex, signaling to S6K1 and 4E-BP1 and rictor-mTOR complex (mTORC2), a rapamycin-insensitive complex that signals to AKT. Although the precise mechanism by which rapamycin inhibits mTOR function is not well understood, rapamycin partially inhibits mTOR function through mTORC1. It has been found that mTORC2 is involved in the regulation of cell survival and actin cytoskeletal organization in a rapamycin-independent manner, and inhibition of mTOR through inhibition of mTORC1 and mTORC2 is probably important for antitumor activity and better efficacy.
US 2007/0112005 describes the fused bicyclic mTOR inhibitors useful in treatment of cancer.
WO 2007/087395 describes unsaturated mTOR inhibitors useful in treatment of cancer.
WO-2008/012326 describes 2,4-substituted quinozolines as lipid kinase inhibitors useful in treatment of P13K-related diseases, such as proliferative diseases, inflammatory diseases, obstructive airways disorder and transplant related diseases.
WO 2006/090169 describes 2,4-diamineo-pyrido-pyrmidine derivatives and their use as mTOR inhibitors.
WO 2007/066099 describes pyrimidine derivatives useful as mTOR kinase inhibitors for anticancer and various other therapeutic treatments involving mTOR kinase.
WO 2007044813 describes pyridopyrimidinone inhibitors of PI3Ka protein kinase for anticancer or other PI3Ka protein kinase related diseases.
US 2005/0222171, WO 2005/070431, WO 2007/0570431 and WO 2007/009773 describe pyrazolo[1,5 a]pyrimidin-7-yl amine derivatives to treat protein kinase dependent diseases.
US 2002/0041880 describes pyrazolo[1,5 a]pyrimidin-7-yl derivatives to inhibit kinase insert domain-containing receptor to block angiogenesis.
WO 1998/003510 describes pyrazolo[1,5 a]pyrimidin-7-yl derivatives to treat corticotrophin releasing factor dependent diseases.
WO 2003/091256 describes pyrazolo[1,5-a]pyrimidine derivatives to treat NAD(P)H oxidase dependent diseases.
WO 2007/044449, WO 2005/077954, WO 2004/022560 and WO 2004/022561 describe pyrazolopyrimidine derivatives as cyclin-dependent kinase dependent diseases.
WO 2004/106341 describes pyrazolopyrimidine derivatives as fungicides.
There is need in the art for small molecule inhibitors of mTOR kinase that block signaling through mTORC1 and mTORC2 as a potential anticancer treatment or a treatment for other cell proliferative disorders.